Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 86675329, compound

HRID 625054Notes

Reaction equation

HRID 625054 reaction equation
Cl.Cl.[CH3:3][C@@H:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[CH2:6][S:5]1.[C:19]([O:23][C:24]([NH:26][C@H:27]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([F:39])[CH:33]=1)[C:28](O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(N(CC)CC)C>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([CH2:31][C@@H:27]([NH:26][C:24](=[O:25])[O:23][C:19]([CH3:20])([CH3:21])[CH3:22])[C:28]([N:16]2[CH2:17][CH2:18][N:13]([C:11]3[C:12]4[C@@H:4]([CH3:3])[S:5][CH2:6][C:7]=4[N:8]=[CH:9][N:10]=3)[CH2:14][CH2:15]2)=[O:29])=[CH:33][C:34]=1[F:39]

Participants

6

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67340403N-Boc-4-chloro-3-fluoro-D-phenylalanineHCID 67459811HCID 67459811, compound

Product 1

HCID 86675329HCID 86675329, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (R)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (30 mg, 0.097 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chloro-3-fluorophenyl)propanoic acid (31 mg, 0.097 mmol) in CH2Cl2 (5 mL) and triethylamine (1 mL) was added HBTU (37 mg, 0.097 mmol). The mixture was stirred at room temperature for 1 hour. The solvent was removed and the residue was dissolved in ethyl acetate (100 mL) and washed with water (5×50 mL). The organic phase was dried and concentrated. The residue was subject to silica gel chromatography, eluting with CH2Cl2/MeOH (50:1) to give tert-butyl (R)-3-(4-chloro-3-fluorophenyl)-1-(4-((R)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (44 mg, 85%). MS (APCI+) [M+H]+ 536.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with water (5×50 mL)
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. washeluting with CH2Cl2/MeOH (50:1)

Sources & evidence

ORD record
ord-24d01efcf76d49cd8280e8baf1514c5c
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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